Neonatal Total Parenteral Nutrition and Long-Term Metabolic Outcomes: An 18-Year Nationwide Cohort Study of 2.3 Million Infants

Background/Objectives: Total parenteral nutrition (TPN) is essential for neonates unable to receive adequate enteral feeding, but its long-term metabolic effects remain uncertain. This study evaluated associations between neonatal TPN exposure, exposure duration, and later endocrinologic or metabolic disorders. Methods: This nationwide cohort included 2,424,716 infants born in South Korea between 2005 and 2010. TPN exposure was identified during the first 28 days of life. The primary outcome was the first occurrence of type 2 diabetes mellitus (T2DM), essential hypertension, dyslipidemia, or obesity during follow-up of up to 18 years. The primary analysis used inverse probability of treatment-weighted (IPTW) Cox models, whereas duration-based associations were evaluated using secondary exploratory multivariable Cox regression. Results: The final cohort included 2,303,567 infants, of whom 7656 received TPN. In the primary IPTW analysis, any neonatal TPN exposure was not associated with either the primary composite outcome (HR 1.01, 95% CI 0.94–1.09; p = 0.801) or T2DM (HR 1.12, 95% CI 0.93–1.35; p = 0.215). In secondary exploratory multivariable analyses, TPN exposure for ≥3 days was associated with T2DM (adjusted HR 2.14, 95% CI 1.34–3.41; p = 0.001), whereas exposure for 1–2 days was not. Conclusions: The primary IPTW analysis showed no significant association between any neonatal TPN exposure and the primary composite outcome or T2DM. The association observed for ≥3 days in secondary exploratory analyses should be regarded as hypothesis-generating.